Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019158 (hepatitis)
 30,205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since January 6th 1994 to december 31 1997. We researched hepatitis C Virus antibodies by second and third generation ELISA in 34,130 bloods donors living in "Sahel Tunisien". 193 were positive (0.56%). Only 171 of them were secondary tested by immunoblot assay (anticore, anti NS5, anti NS3, anti NS4). Which was positive in 53 cases (30.9%); in determined (presence of only one antibody) in 78 cases (45.6%) and negative, in 40 cases (23.3%). There was a significant relation between a ratio over than 2.5 in ELISA and immunoblot positivity. Immune response to different hepatitis virus antigens were heterogeneous with predominant in determined profile. (78/171 cases). Most of donors of the last profile had either anti NS5 (32/78) or anti NS3 (33/78) and we excluded them even through usually negative in P.C.R and associated with a very low risk of contamination.
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PMID:[Hepatitis C virus antibodies in 34130 blood donors in Tunisian Sahel]. 1089 44

Infection with the hepatitis C virus (HCV) is the major cause of non-A, non-B hepatitis worldwide. The viral genome, a positive-sense, single-stranded, 9.6-kb long RNA molecule, is translated into a single polyprotein of about 3,000 amino acids. The viral polyprotein is proteoytically processed to yield all the mature viral gene products. The genomic order of HCV has been determined to be C-->E1-->E2-->p7-->NS2-->NS3-->NS4A-->NS4B-->NS5A++ +-->NS5B. C, E1, and E2 are the virion structural proteins. Whereas the function of p7 is currently unknown, NS2 to NS5B are thought to be the nonstructural proteins. Generation of the mature nonstructural proteins relies on the activity of viral proteinases. Cleavage at the NS2-NS3 junction is accomplished by a metal-dependent autocatalytic proteinase encoded within NS2 and the N-terminus of NS3. The remaining downstream cleavages are effected by a serine proteinase contained also within the N-terminal region of NS3. NS3, in addition, contains an RNA helicase domain at its C-terminus. NS3 forms a heterodimeric complex with NS4A. The latter is a membrane protein that acts as a cofactor of the proteinase. Although no function has yet been attributed to NS4B, NS5A has been recently suggested to be involved in mediating the resistance of the HCV to the action of interferon. Finally, the NS5B protein has been shown to be the viral RNA-dependent RNA polymerase. This article reviews the current understanding of the structure and the function of the various HCV nonstructural proteins with particular emphasis on their potential as targets for the development of novel antiviral agents and vaccines.
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PMID:Biochemical and immunologic properties of the nonstructural proteins of the hepatitis C virus: implications for development of antiviral agents and vaccines. 1089 33

The identification of antivirals and vaccines against hepatitis C virus (HCV) infection is hampered by the lack of convenient animal models. The need to develop surrogate models has recently drawn attention to GB virus B (GBV-B), which produces hepatitis in small primates. In a previous study in vitro, it was shown that GBV-B NS3 protease shares substrate specificity with the HCV enzyme, known to be crucial for virus replication. In this report, GBV-B NS3 activity on GBV-B precursor proteins has been analysed in a cell-based system. It is shown that mature protein products are obtained that are compatible with the cleavage sites proposed on the basis of sequence homology with HCV and that GBV-B NS4A protein is required as a cofactor for optimal enzymatic activity. Experiments in vitro supported by a structural model mapped the region of NS4A that interacts with NS3 and showed that the GBV-B cofactor cannot be substituted for by its HCV analogue.
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PMID:Processing of GB virus B non-structural proteins in cultured cells requires both NS3 protease and NS4A cofactor. 1095 Sep 75

Hepatitis C virus (HCV) is the major etiologic agent of non-A, non-B hepatitis. HCV infection frequently causes chronic hepatitis, which progresses to liver cirrhosis and hepatocellular carcinoma. Since the discovery of HCV in 1989, a large number of genetic analyses of HCV have been reported, and the viral genome structure has been elucidated. An enveloped virus, HCV belongs to the family Flaviviridae, whose genome consists of a positive-stranded RNA molecule of about 9.6 kilobases and encodes a large polyprotein precursor (about 3000 amino acids). This precursor protein is cleaved by the host and viral proteinase to generate at least 10 proteins: the core, envelope 1 (E1), E2, p7, nonstructural (NS) 2, NS3, NS4A, NS4B, NS5A, and NS5B. These HCV proteins not only function in viral replication but also affect a variety of cellular functions. HCV has been found to have remarkable genetic heterogeneity. To date, more than 30 HCV genotypes have been identified worldwide. Furthermore, HCV may show quasispecies distribution in an infected individual. These findings may have important implications in diagnosis, pathogenesis, treatment, and vaccine development. The hypervariable region 1 found within the envelope E2 protein was shown to be a major site for the genetic evolution of HCV after the onset of hepatitis, and might be involved in escape from the host immunesurveillance system.
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PMID:Genome of human hepatitis C virus (HCV): gene organization, sequence diversity, and variation. 1125 51

An inducible in vitro cell culture system was developed to assay HCV replication by direct biochemical means. A transcription plasmid containing a T7 promoter at the 5' end, full-length cDNA of the HCV genome, a ribozyme sequence from the antigenomic strand of hepatitis delta virus and a T7 terminator was prepared. To facilitate high-level transcription of HCV RNA, HepG2 cells were infected with replication deficient adenovirus containing the T7 RNA polymerase gene and later transfected with the transcription plasmid containing the full-length HCV genome. This transfection-based cell culture system expressed high levels of HCV structural (core, El and E2) and non-structural proteins (NS3 and NS5B) detectable by Western blot and immunofluorescence assays. Production of HCV RNA transcripts and presence of replicative negative strand of HCV was confirmed by ribonuclease protection assay indicating replication of HCV in the transfected HepG2 cell. The transfected HepG2 cells assembled 50-60 nm virus-like particles, which could be aggregated by anti-E2 antibodies. This model can be utilized for studying mechanisms of HCV replication, assembly of HCV particles and to test potential anti-HCV compounds.
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PMID:Inducible model to study negative strand RNA synthesis and assembly of hepatitis C virus from a full-length cDNA clone. 1133 40

High concentrations of nitric oxide (NO) are generated by the inducible form of the enzyme nitric oxide synthase (iNOS), which is expressed in activated macrophages and in hepatocytes. Increased expression of iNOS in hepatocytes or macrophages might be expected in chronic HCV liver disease and HIV infections. This might in turn be reflected in increased serum NO levels in these two conditions. In view of the discrepant findings in published reports, we measured serum NO levels in a large number of chronic HCV-infected patients and patients with chronic HIV infections with or without AIDS-related opportunistic infection. We also localized HCV and iNOS antigens by immunohistochemistry, in liver biopsy tissue from patients with chronic HCV-related hepatitis, HCV-related cirrhosis, and HCV-related hepatocellular carcinoma. A group of 121 subjects with serological evidence of HCV with or without HIV infection were studied. These were compared with 14 controls without HIV or HCV disease (group A). Among the subjects with HCV, 35 were negative for HIV (group B), 66 were HIV positive (group C), and 20 had AIDS-related opportunistic infection (group D). The serum NO concentration was determined by the Brucine method. A well-characterized commercially available antibody (HCV88) directed against a synthetic NS3 peptide fragment of HCV, which localizes to the hepatocyte nuclei, and an antibody to human macrophage iNOS, were both used to detect these proteins in liver biopsy tissue by immunohistochemistry. Mean serum NO values in HIV negative/HCV negative control patients (group A) (54.6+/-12 microM) were similar to those in HIV negative/HCV positive patients (group B) (55.0+/-13 microM) and HIV positive without AIDS-related disease/HCV positive patients (group C) (47.2+/-25 microM). By contrast, the mean serum NO (70.1+/-24 microM) was significantly increased in HCV-positive patients with AIDS-related infection (group D) compared to controls (P = 0.02). HCV NS3 and iNOS antibody staining hepatocytes were not detected in any of the control non-HCV-infected biopsy samples. In early chronic HCV hepatitis (fibrosis scores F0-F2), HCV NS3 antigen localized focally to only a small number of hepatocytes. In cirrhosis (fibrosis score F4) with or without hepatocellular carcinoma, the majority of hepatocyte nuclei stained positively with HCV NS3 antibody. The majority of hepatocytes in chronic HCV hepatitis expressed iNOS, irrespective of histological disease severity. The staining was present uniformly in the cytoplasm. In chronic HCV and HIV coinfection, the pattern and number of iNOS staining cells were similar to that in patients with chronic HCV infection alone. In conclusion, there is widespread expression of iNOS in hepatocytes in chronic HCV liver disease, irrespective of liver disease stage. However, elevated NO levels in serum were related only to active AIDS-related bacterial, protozoan, and fungal infections, rather than to chronic viral infection with HCV or HIV alone. NO may play a role in the local control of chronic viral infections at tissue level, but this is not reflected in serum levels.
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PMID:Nitric oxide and chronic HCV and HIV infections. 1134 51

GB viruses A and B (GBV-A and GBV-B) are members of the Flaviviridae family and are isolated from tamarins injected with serum from a human hepatitis patient. Along with a related human virus, GB virus C, or alternatively, hepatitis G virus (GBV-C/HGV), the three viruses represent the GB agents. Of the three viruses, GBV-B has been proposed as a potential surrogate model for the study of hepatitis C virus (HCV) infections of humans. GBV-B is phylogenetically most closely related to HCV and causes an acute, self-resolving hepatitis in tamarins as indicated by an increase in alanine aminotransferase and changes in liver histology. Similarities between GBV-B and HCV are found at the nucleotide sequence level with the two viruses sharing 28% amino acid homology over the lengths of their open reading frames. Short regions have even higher levels of homology that are functionally significant as shown by the ability of the GBV-B NS3 protease to cleave recombinant HCV polyprotein substrates. The shared protease substrate specificities suggest that GBV-B may be useful in testing antiviral compounds for activity against HCV. Although there are numerous similarities between GBV-B and HCV, there are important differences in that HCV frequently causes chronic infections in people, whereas GBV-B appears to cause only acute infections. The acute versus chronic course of infection may point to important differences between the two viruses that, along with the numerous similarities, will make GBV-B in tamarins a good surrogate model for HCV.
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PMID:GB virus B as a model for hepatitis C virus. 1140 17

Although hepatitis C virus (HCV) is a major cause of non-A non-B hepatitis, its pathogenic role in fulminant hepatitis remains controversial. A 32-year-old man contracted hepatitis. Serum ALT concentration was reached to 6,970 IU/L, the lowest prothrombin time value was 16% and jaundice and stage II encephalopathy were developed. HCV RNA was detected in this patient by reverse transcription polymerase chain reaction in sera at the acute phase, and it was undetectable during the remission phase when anti-HCV was found. The entire genome of infected HCV was recovered, cloned, and sequenced from this patient, and compared with the clones of six other chronic hepatitis patients. Phylogenetic analysis revealed a clustering around genotype 2a and a deviation from the other 2a chronic hepatitis strains. Calculating the genetic distance in each subgenomic region revealed that the 5'untranslated region (5'UTR), core, nonstructural (NS) 3, and NS5A were severely deviated. Of 20 clones of the hypervariable region (HVR), 17 showed an identical sequence with the others showing a difference of only one amino acid. HCV was isolated from a fulminant hepatitis patient and its entire genome was recovered; a clustering around genotype 2a was observed, but the sequence deviated especially in 5'UTR, core, NS3, and NS5A; and monoclonality of the HVR sequence was found not only in the fulminant hepatitis patient but in a certain percentage of chronic hepatitis patients.
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PMID:Sequence analysis of hepatitis C virus isolated from a fulminant hepatitis patient. 1142 23

Hepatitis C virus (HCV), discovered in 1989, is the major causative agent of parenteral non-A, non-B hepatitis worldwide. Following the development of a method of diagnosing HCV infection, it became apparent that HCV frequently causes chronic hepatitis. Persistent infection with HCV is implicated in liver cirrhosis and hepatocellular carcinoma. Current worldwide estimations suggest that more than 170 million people have been infected with HCV, an enveloped positive single-stranded RNA (9.6-kilobases) virus belonging to the Flaviviridae. The HCV genome shows remarkable sequence variation, especially in the hypervariable region 1 of the E2 protein-encoding region, and globally, HCV appears to be distributed with more than 30 genotypes. Complicated "quasispecies" and frequent mutations of viral genomes have also emerged. The HCV genome encodes a large polyprotein precursor of about 3,000 amino acid residues, and this precursor protein is cleaved by the host and viral proteinases to generate at least 10 proteins in the following order: NH2-core-envelope (E1)-E2-p7-nonstructural protein 2 (NS2)-NS3-NS4A-NS4B-NS5A-NS5B-COOH. These viral proteins not only function in viral replication but also affect a variety of cellular functions. Although several explanations have been proposed, the mechanisms of HCV infection and replication in targeted cells, the mechanism of persistent viral infection, and the pathogenesis of hepatic diseases (hepatitis or hepatocellular carcinoma) are all poorly understood. A major reason why these mechanisms remain unclear is the lack of a good experimental HCV replication system. Although several classical trials using cultured cells have been reported, several new, more promising experimental strategies (generations of infectious cDNA clone, replicon, animal models, etc.) are currently being designed and tested, in order to resolve these problems. In addition, new therapies for chronic hepatitis have also been developed. The enormous body of information collected thus far in the field of HCV research is summarized below, and an overview of the current status of HCV molecular virology of HCV is provided.
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PMID:Molecular virology of hepatitis C virus. 1143 27

AIM:To detect HCV infection in patients with HCC and other liver diseases by the immunohistochemical method.METHODS: The expression of HCV antigen was identified by means of LSAB (labelled streptavidin-biotin) method using anti-NS3 monoclonal antibody.RESULTS: The positive rates of HCV antigen in the three groups of HCC, liver cirrhosis and hepatitis were 13.5% (7/52), 12.5% (2/16), and 10% (4/40) respectively, while in the samples from patients with constitutional jaundice and normal liver samples, no HCV antigen was found. HCV antigen could be seen in the nuclei and/or cytoplasms of carcinoma cells and/or pericancerous hepatocytes. In HCC, HCV antigen was more often seen in nuclei than in cytoplasms. The positive rate of HCV antigen in pericancerous tissues was higher than that in cancerous tissues.CONCLUSION: HCV is associated with HCC,and HCV infection enhances the development of liver diseases. HCV affects the initiative period of HCC and induces the malignant phenotypic alteration of hepatocytes.
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PMID:Immunohistochemical detection of HCV infection in patients with hepatocellular carcinoma and other liver diseases. 1181 35


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